Many cases of acute gastroenteritis in Man and his domestic animals are not associated with well recognized bacterial or viral pathogens. Several lines of investigation have incriminated members of the "normal" intestinal flora, particularly Escherichia coli, as the culprits. Our proposed research attempts to define the capacity of these microorganisms to cause disease and to define ways for the development of preventive measures. Our research has focused upon the genetic basis for enterotoxin production and specific tissue adhesive properties of epidemic strains of E. coli. In all instances in which thorough analysis has been performed both the capacity to elaborate enterotoxin (Ent), as well as the ability to specifically adhere to small bowel epithelial cells (Kad) has been associated with bacterial plasmids. Ent and Kad plasmids have been transmitted into various E. coli genetic backgrounds and their contribution to pathogenicity examined in suitable animal models. These plasmids are indivdually innocuous but, in combination, are sufficient to convert some, but not all, E. Coli strains to an enterotoxin production and the Kad specified cellular appendages. BIBLIOGRAPHIC REFERENCES: So, M., J.H. Crosa and S. Falkow. 1975. Polynucleotide sequence relationships among Ent plasmids and the relationship between Ent and other plasmids. J. Bacteriol. 121:234-238. So. M., J.F. Crandell, J.H. Crosa and S. Falkow. 1975. Extra-chromosomal determinants which contribute to bacterial pathogenicity. Microbiology 1974. ed. D. Schlessinger, ASM, Washington, D.C. pp 16-26.